This study examines the issue of silent strokes in the relationship between the structural stability of atherosclerotic carotid plaque and the development of nonmotor symptomatology, including brain atrophy and cognitive decline. It addresses the question of the role of carotid emboli in silent stroke and their cognitive sequelae. The study uses human carotid endarterectomy patients to study three specific aims. The first uses ultrasound to relate plaque elasticity and its development of mechanical strain features with pulsation and the histopathophysiology of the plaque for ulcer, hemorrhage and thinning of stabilizing fibrous cap at the point of these mechanical strain features. The second examines ultrasound detected elasticity strain features in the plaques and the presence of transcranial Doppler TCD detectable microemboli. The third looks at ultrasound strain deficits, microemboli, cognitive decline and brain MRI evidence of focal and generalized atrophy. Understanding the structural plaque abnormalities, which render a carotid plaque mechanically unstable and at risk of embolization will demonstrate a pathophysiologic mechanism in individuals who are likely to suffer not only classic episodic major strokes, but also functional progressive decline from the contribution of microemboli to cerebral silent stroke and cognitive decline. PUBLIC HEALTH RELEVANCE: Cerebrovascular disease remains a major health problem with increasing impact on an aging population. Studies suggest that clinical and silent stroke affects 11 million Americans per year. Vascular aging from atherosclerosis is a major contributor to this problem. For this reason, we propose a study of carotid atherosclerosis developing novel markers for carotid plaque instability which may result in the presence of multiple microemboli, which in turn may contribute to increased symptomatology, both classic strokes, as well as, cognitive decline. If successful, this study will greatly increase our understanding of the pathophysiology of symptoms from atherosclerosis, as well as, lead to the development of potential new measures to detect this disorder noninvasively.